The human malaria pathogen, Plasmodium falciparum, replicates more than 10-fold every 48 hours and has a large requirement for rapid protein translation, so the loss of function of factors involved in protein biosynthesis could be detrimental to the parasites. Aminoacyl-tRNA synthetases (aaRSs) are enzymes that are key to the production of substrates for protein translation, an event that occurs in three cellular components of the parasite: the cytosol, the mitochondrion, and a remnant chloroplast called the apicoplast. P. falciparum expresses two forms of the tryptophanyl-tRNA synthetase (TrpRS) gene, and by analysing the subcellular localization of the two isoforms we have shown that one localises to the apicoplast and the other to the cytosol. This enzyme is an attractive drug target in malaria parasites as several protein translation inhibitors have been developed as antimalarial drugs. To test for inhibition in malaria parasites, TrpRS inhibitors and analogues were identified and screened according to their pharmacokinetics properties. Assessment of dose-response curves reveal that several of these bacterial-type TrpRSs inhibitors effectively arrest parasite growth at low µM range. One, Indolmycin, kills with a delayed death effect characteristic of apicoplast inhibitors. We are now testing the effect of these compounds in vitro on the aminoacylation activity of the Plasmodium TrpRSs. We anticipate that the major differences between the host and the parasite TrpRSs will allow us develop parasite-specific inhibitors that may be used as starting points for drug development.